Monitoring Drug Loading and Releasing in MIL-88B(Fe) Films on … · 2020. 4. 28. · Monitoring Drug Loading and Releasing in MIL-88B(Fe) ... SPR allows real-time, label free detection
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Trenton Nguyen, Hao Pham and Dr. Fangyuan Tian
Department of Biomedical Engineering and Department of Chemistry
ACKNOWLEDGEMENTS
This research was supported by the National Institute of General Medical
Sciences of the National Institutes of Health under Award Numbers;
5UL1GM118979; 5TL4GM118980; 5RL5GM118978. The content is solely
the responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health.
Monitoring Drug Loading and Releasing in MIL-88B(Fe) Films
on Modified Gold Substrates using Surface Plasmon Methods
ABSTRACTCoronary Artery disease (CAD) is a major leading
cause of death in the United States. Characterized by
plaque narrowing the blood vessel, people with CAD
have a higher chance of experiencing heart attack and
stroke. Our research studies the effects of using MIL-
88B, a porous structure of the class: Metal Organic
Framework (MOF) as a porous inorganic coating on
drug eluting stent (DES), to prevent CAD and minimize
restenosis and thrombosis effects. MIL-88B was
synthesized under a solvo-thermo method and used for
UV-Vis to see drug delivery properties while
implementation of MIL-88B on gold was used as a
model to see the binding of Ibuprofen on MIL-88B as
well as the binding of 16-Mercaptohexadecanoic acid
(MHDA) on gold for SPR experiments. Our results
confirmed the successful preparation of ibuprofen
loaded MIL-88B film on MHDA functionalized gold
substrate.
CONCLUSIONWe confirmed the encapsulation of ibuprofen within the
porous MIL-88B structures by optical spectroscopic
studies. The drug loading capacity of the testing Fe-MIL
material was found to be about 19.5 wt% for ibuprofen
delivery. SPR results showed successful binding of a
MHDA SAM on clean gold surface within a few minutes.
Additionally, we prepared a uniform MIL-88B film on a
MHDA modified Au surface via covalent bonding. The
successful encapsulation of ibuprofen in MIL-88B was
confirmed by a significant change in SPR resonance
response in the in situ studies. Following hexane wash,
no significant decrease in SPR signal was observed for
the ibuprofen-loaded MIL-88B film. This confirmed
ibuprofen was encapsulated inside of MIL-88B cages
not being adsorbed on the outer surface.
REFERENCES
1. Novel Route to Size-Controlled Fe–MIL-88B–NH2 Metal–
Organic Framework Nanocrystals
Minh-Hao Pham, Gia-Thanh Vuong, Anh-Tuan Vu, and
Trong-On Do. Langmuir 2011 27 (24), 15261-15267 DOI:
10.1021/la203570h
2. Tuning Crystal Structures of Iron-Based Metal-Organic
Frameworks to Control Drug Delivery Applications
Pham, Hao; Ramos, Kimberly; Sua, Andy; Acuna, Jessica;
Slowinska, Katarzyna; Nguyen, Trenton; Bui, Angela;
Weber, Mark; Tian, Fangyuan. ACS Omega 2019, submitted
RESULTS
METHODSSynthesis:
MIL-88B is synthesized by mixing a set amount of
metal, Iron (III) Chloride with ligand, Terephthalic acid in
DMF solvent. After heating for about 12 hours, a
network of metal framework developed with porous
centers.
Surface Plasmon Resonance (SPR)
SPR allows real-time, label free detection of
biomolecular interactions.
Self Assembled Monolayer (SAM):
The formation of MHDA SAM on clean gold surface
was monitored using SPR. Similarly, the binding of MIL-
88B to MHDA along with ibuprofen loading was studied
using SPR.
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
245 250 255 260 265 270 275 280 285
Ab
sorb
ance
WaveLength (nm)
Ibuprofen Absorption
Ibuprofen before MIL88BIbuprofen after MIL88B
y = 0.8865xR² = 0.9983
0.000.200.400.600.801.001.201.401.601.802.00
0.0 0.5 1.0 1.5 2.0 2.5
Ab
sorb
ance
Concentration
Ibuprofen/Hexane Standard Curve
Terephthalic Acid
+
X-ray Powder Diffraction (XRD)
PXRD patterns of MIL-
88B at the condition of
i) as-synthesized,
ii) after solvent
exchange
iii) after loading with
ibuprofen, in comparison to
the PXRD patterns of
iv) pure ibuprofen.
UV-Vis Spectroscopy
Infrared Spectroscopy
Surface Plasmon Resonance
65
65.5
66
66.5
67
67.5
0 200 400 600 800 1000 1200
Res
on
ance
Un
it (
RU
)
Time (Seconds)
Measuring Channel Reference Channel
MHDA MIL-88BIbuprofen
Hexane
19.5 wt% of ibuprofen in MIL-88B
𝐿𝐶 =𝐶0 − 𝐶𝑡 ∗ 𝑉
𝑚
Hexane
Scanning
Electron
Microscopy
(SEM)
ATR-IR spectra of
a) pure ibuprofen,
b) pristine Fe-MIL-88B,
c) ibuprofen loaded Fe-MIL-
88B
SEM images of
a) clean gold
b) MIL-88B crystals
on MHDA-modified
Au surface
c) ibuprofen loaded
MIL-88B crystals
d) MIL-88B after
releasing ibuprofen
in PBS.
FTIR spectra of
a) Au surface,
b) MHDA SAM modified Au
surface,
c) Fe-MIL-88B thin film on a
MHDA-functionalized Au
substrate,
d) ibuprofen loaded Fe-MIL-
88B thin film
e) Fe-MIL-88B thin film after
drug releasing.
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